Dual modulus balloon for interventional procedures

ABSTRACT

A device for interventional surgical or medical procedures is presented. The device is generally in the form of a balloon and is used to position itself or other working elements up against or through lumen walls in the body. The balloon is comprised of at least two materials of different elastic modulus, which allows for a flexible but relatively non-distensible, unfolding component of the balloon as well as an elastomeric, inflatable component of the balloon. The elastomeric component is fixedly attached to the flexible but relatively non-distensible component and together they form a pressure vessel that can be inflated within the lumens of the body.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.12/711,141 (Attorney Docket No. 021621-002720US), filed on Feb. 23,2010, which is a divisional of U.S. application Ser. No. 11/858,797(Attorney Docket No. 021621-002710US), filed on Sep. 20, 2007, whichclaims the benefit of provisional U.S. Application No. 60/826,478(Attorney Docket No. 021621-002700US), filed on Sep. 21, 2006, the fulldisclosures of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical methods and devices.More particularly, the present invention relates to intraluminalcatheters with balloons having segments with different material moduli,which upon inflation improve apposition of tools against luminalstructures, such as blood vessel walls or walls of other body lumenssuch as bronchi or the urethra.

Coronary artery disease is the leading cause of death and morbidity inthe United States and other Western societies. In particular,atherosclerosis in the coronary arteries can cause myocardialinfarction, commonly referred to as a heart attack, which can beimmediately fatal or, even if survived, can cause damage to the heartwhich can incapacitate the patient. Other coronary diseases which causedeath and incapacitation include congestive heart failure, vulnerable orunstable plaque, and cardiac arrhythmias. In addition to coronary arterydisease, diseases of the peripheral vasculature can also be fatal orincapacitating. Vascular occlusions, blood clots and thrombus mayocclude peripheral blood flow, leading to tissue and organ necrosis.Deep vein thrombosis in the legs can, in the worst cases, requireamputation. Clots in the carotid artery can embolize and travel to thebrain, potentially causing ischemic stroke. Diseases causing narrowingof a lumen in the body are not limited to blood vessels. As examples,but by no means limiting, chronic obstructive pulmonary disease (COPD)and cancerous tumors may cause constriction of bronchi in the lungs, andprostate cancer or benign prostatic hyperplasia (BPH) may causeconstriction of the urethra.

Percutaneous or endoscopic interventional procedures are very common inthe United States and other countries around the world. Intravascularcatheter systems are used for procedures such as balloon angioplasty,stent placement, atherectomy, retrieval of blood clots, photodynamictherapy, and drug delivery. All of these procedures involve theplacement of long, slender tubes known as catheters into arteries,veins, or other lumens of the body in order to provide access to thedeep recesses of the body without the necessity of open surgery.

Percutaneous procedures also include those that place working ends ofcatheters into body cavities such as the ventricles or atria of theheart. The placement of needles into the heart wall from within aventricle can also be performed during catheter-based procedures asdescribed in the previous paragraph.

Medical devices used in catheter procedures often include a workingcomponent at or near the distal (farthest from the operator) end of thecatheter that is operated by hydraulic, pneumatic, or other mechanicalmeans. These systems can sometimes include a working component such as amicroneedle on one side of the catheter or at the distal end of thecatheter that must be apposed against the wall of the lumen.

Such catheters can also benefit the treatment of other lumens in thebody. For example, the sinus passages leading from nasal openings to thesinuses or pharynx may become inflamed, for example after sinus surgeryor in the case of nasal polyposis. In these cases, systems similar tothose used in percutaneous procedures may also require apposition of oneside of the working end against the lumen wall.

Of particular interest to the present invention, catheters carryingmicroneedles capable of delivering therapeutic and other agents deepinto the adventitial layer surrounding blood vessel lumens have beendescribed U.S. Pat. No. 6,547,803, issued on Apr. 15, 2003, and inco-pending application Ser. No. 09/961,080, filed on Sep. 20, 2001, and09/961,079, also filed on Sep. 20, 2001, all of which have commoninventorship with but different assignment than the present application,the full disclosures of which are incorporated herein by reference.

The designs described in the issued patent and copending applicationshave numerous advantages. The microneedles are delivered in a directionwhich is substantially perpendicular to the axis of the catheter, thusmaximizing the depth of needle penetration into the wall and reducingtrauma and injury. Moreover, by locating the needles on the exterior ofan expanding involuted surface, the needles can be injected into tissuefully up to their point of attachment to the catheter, furthermaximizing the needle penetration depth which may be achieved.

Such deep needle penetration depends at least partly, however, on havingan expansible surface structure chosen to accommodate the size of thelumen being treated. As lumen sizes may vary significantly, it may benecessary to maintain an inventory of differently sized catheters toaddress all patients and conditions.

While functional, the need to maintain and manufacture an inventory ofcatheters with differently sized balloons is costly. Moreover, shouldthe physician choose the wrong balloon for a procedure, it may becomenecessary to replace the balloon with a second balloon catheter, furtherincreasing the cost and time necessary to perform the procedure.

For these reasons, it would be desirable to provide improved devices andmethods for transmitting appositional force from one side of acatheter-based balloon to the other opposite side. In particular, itwould be desirable to provide intravascular and other intraluminalcatheters having balloons or other inflation structures for advancingneedles and other tools toward or into adjacent luminal walls, where theinflation structures are selectively inflatable to different sizes inorder to accommodate different luminal diameters and/or to penetrateneedles to different depths. Preferably, such selective inflation wouldbe accomplished by delivering different pressures or volumes ofinflation media to the inflatable structures. It is a further objectivethat the methods be simple and economic to implement and be useful witha wide range of vascular and other medical catheters. At least some ofthese objectives will be met by the inventions described hereinafter.

2. Description of the Background Art

Catheters used to slide microneedles through vessel walls are describedin U.S. Pat. No. 6,547,803, issued on Apr. 15, 2003, and in co-pendingapplication Ser. No. 09/961,080, filed on Sep. 20, 2001, and 09/961,079,also filed on Sep. 20, 2001, all of which have common inventorship withbut different assignment than the present application, the fulldisclosures of which are incorporated herein by reference.

BRIEF SUMMARY OF THE INVENTION

The present invention provides catheters with a single balloon or otherinflatable actuator which is inflated at a first pressure to unfurl ordeploy a first portion of the balloon, where delivery of an additionalinflation pressure or volume expands or otherwise deploys a secondportion of the balloon wall to a size larger than or a configurationdifferent than that achievable by inflation or unfurling of the firstportion of the balloon wall alone. Multiple components may be combinedinto the same balloon or pressure component, such that one part of thewall is non-distensible and another part of the wall is compliant orelastomeric, such that a single inflation step, whether it involvesvolume or pressure, may be useful to activate both the non-distensibleand compliant structures simultaneously or in series.

The present invention also provides catheters and methods for deployinginterventional tools in blood vessels and other body lumens. Theinterventional tools are typically needles which are penetrated into aluminal wall, but could be other structures such as atherectomy blades,optical fibers for delivering laser energy, mechanical abrasion anddrilling components, and the like. The catheters comprise a catheterbody having a proximal end and a distal end. The needle or otherinterventional tool is coupled to a distal portion of the catheter, andan inflatable structure is provided on or near the distal portion of thecatheter body in order to advance the tool laterally relative to an axisof the catheter body. The inflatable structure may comprise two or morediscrete regions which deform or inflate at different, typicallysuccessive inflation pressures. Usually, the regions will have differentelasticities (where one may be substantially non-elastic ornon-distensible), but in certain embodiments the regions could haveidentical elasticities where inflation of one or more of the regionsbelow threshold pressure is prevented by tethers or other restraintswhich yield or break above said threshold pressure(s). By providing atleast one non-distensible region, the non-distensible region can befully inflated at relatively low pressures to a preselected size. Ifadditional force or lateral displacement is needed, the inflatablestructure can then be inflated beyond the first inflation threshold inorder to expand one or more additional regions of the balloon, where theadditional regions may have the same inflation characteristics ordifferent inflation characteristics.

The regions of differing elasticity in the inflation structure can beachieved and fabricated in a variety of ways. In the exemplaryembodiments below, the regions are formed in an edge-to-edge manner oralong an overlapping border region using conventional masking anddeposition techniques. It will be appreciated that the regions couldalso be formed by layering materials of differing elasticities,providing layers having different thicknesses, providing reinforcementfibers or materials which create regions of different elasticity withina matrix of the same material, providing tethers and other stretchableor breakable elements within regions of the inflation structure whichyield or break when tension is applied above threshold levels, and thelike.

The interventional tool may be mounted directly on the catheter body,but in the illustrated embodiments is mounted on the inflatablestructure itself. It will be appreciated that more than oneinterventional tool may be mounted on the catheter, and that suchmultiple tools may be mounted directly on the catheter body, on theinflatable structure, or both.

By “non-distensible,” it is meant that the material of the balloon willbe inflatable from a lower profile or volume configuration to anexpanded or higher profile or volume configuration. Once at the highervolume, expanded configuration, however, the material will no longerstretch or expand to any reasonable extent (typically less than 200%elongation in any direction prior to rupture) even though the inflationpressure can be raised significantly above the threshold pressure whichachieves the higher volume inflation. By “elastomeric” it is meant thatthe material displays elasticity as more pressure is applied. Usually,there will be minimum or nominal stretching or expansion at or below thethreshold pressure, but significant stretching and expansion atinflation pressures above the threshold pressure (typically at least 50%elongation in any direction prior to rupture, often at least 300%elongation in any direction prior to rupture, and usually at leastgreater than the elongation achievable by the non-distensible materialprior to rupture). Additionally, the elastomeric materials will continueto stretch, usually in a nonlinear manner as pressure is increased abovethe threshold level.

The present invention further provides methods for treating body lumenscomprising introducing one or more interventional tools to the bodylumen. An inflatable structure is inflated to a first pressure below athreshold pressure to advance the tool laterally to a first “maximum”distance which will not be exceeded so long as the pressure ismaintained below the threshold pressure level. After inflation to thefirst pressure, if it is desired to further laterally advance theintervention tool, the inflatable structure may be inflated to apressure which exceeds the first threshold pressure to further laterallyadvance the tool beyond the first maximum distance. The tool may beadvanced to a second maximum distance, or alternatively may beincrementally advanced if the inflatable structure includes an elasticregion which expands in linear or nonlinear proportion to the inflationpressure.

In a first aspect of the present invention, a medical device comprises atubular member with a proximal and distal end, an involuted balloon ator near the distal end of the medical device with a working componentembedded in the involuted segment, an ability to inflate the involutedballoon to deploy the working component, and a material with lowermodulus than the involuted balloon material, affixed to and comprisingpart of the wall of the involuted structure, such that the lower modulusmaterial may expand at a different rate and create an anchoring oropposing force to the working component. The material with lower modulusmay be affixed in one or more ways to the material with higher modulus.In most cases, the lower modulus material resembles a “patch”, ormembrane structure, on the opposite side of the involuted structure fromthe working component.

In a second aspect of the present invention similar to the first aspect,the medical device comprises a tubular member with proximal and distalend, a working component at the distal end, and the requirement to placesuch working component asymmetrically against the wall of a body lumen.The attachment of the lower modulus “patch” to one side of the workingcomponent end structure allows for the asymmetric deployment of theworking component via hydraulic or pneumatic pressurization of the lowermodulus patch, or membrane, with respect to the higher modulus flexiblebut relatively non-distensible structure to which it is attached.

In a third aspect of the present invention, the working end of thetubular medical device may require particular positioning within a bodylumen. Multiple low-modulus “patch”, or membrane, structures may beaffixed to a higher modulus structure such that the patches may beinflated individually or simultaneously in order to position the tip ofthe medical device appropriately within the body lumen.

In a fourth aspect of the present invention, the lower modulus “patch”or membrane structure and the higher modulus flexible but relativelynon-distensible “anchor” structure meet at a joint that is formedbetween and consists only of the two materials constituting the patchand the anchor, respectively. The seal formed between the two materialsat this joint is free from leakage below a particular amount ofpressurization, and thus integrates the two materials to form onepressure vessel with wall components comprised of each material.

In an exemplary embodiment, the low-modulus material (the patch) is aflexible material such as silicone rubber or polydimethylsiloxane(PDMS). The high-modulus material (which can form the anchor to thepatch or membrane) is a more flexible but relatively non-distensiblepolymer such as poly-paraxylylene (parylene N, C, or D). The low modulusmaterial may be generally in a round and flat configuration, but mayhave more complex shape. The high modulus material is designed to have a“hole” in it approximately the size of the patch material, with someoverlap to accommodate the attachment joint. The silicone patch, ormembrane, and parylene flexible but relatively non-distensible materialmay be fixedly attached by polymeric encapsulation or polymericadhesion, a process in which the parylene is vapor-deposited directlyonto three substrates at once: a removable mold material adjacent to thesilicone patch, the edge or border region of the silicone patch, and aremovable (masking) material that protects the remainder of the siliconepatch from being coated. When both removable materials are removed (e.g.by dissolution), the remaining structure is a parylene substrate with anaffixed silicone patch, in which the joint formed between the twocomponent structures consists only of the two constituent materials thatcomprise the individual components.

In the embodiment described above, the silicone patch may be on the backside of a folded balloon structure. The folded balloon structure isprimarily comprised of parylene, but the patch comprises at least someof the surface area of the balloon. When the balloon is inflated, theflexible but relatively non-distensible structure unfolds, and then theelastomeric silicone expands due to pressurization. The flexible butrelatively non-distensible parylene material unravels, but stretchesmuch less than the silicone, thus forming the dual modulus balloon.

In a further embodiment of the present invention, polymer vapordeposition may be used to form both the flexible but relativelynon-distensible material component and a joint or interfacial regionbetween the flexible component and the elastomeric component. Polymervapor deposition of parylene or other suitable polymer typically beginswith sublimation of a parylene dimer or other precursor at an elevatedtemperature in a low pressure chamber. The dimer vapor is then cleavedinto monomer vapor as it travels through a higher temperature furnace.The monomer vapor travels into a deposition chamber, also held undervacuum, but at ambient temperature, at which point the monomer moleculesrapidly lose energy and polymerize on surfaces within the depositionchamber. This process creates parylene coatings on components placedinto the deposition chamber. Parylene coatings are usually nearlyuniform, but thickness of the films varies based on the thermalproperties of the system, the amount of dimer used, the intricacy ofgeometric surfaces placed into the deposition chamber, and the pressureat which the coating process is performed. By properly masking andcreating layers, as described hereinafter, the flexible component andthe elastomeric component may be joined as the flexible component isbeing formed. Other variables of the coating process also add tovariance in the parylene coating characteristics.

In further exemplary embodiments, the lower-modulus material may bepolyether block amide (Pebax), neoprene, Silastic®, chronoprene, C-flex,latex or other elastomeric materials.

In further exemplary embodiments, the higher-modulus material may be athermoplastic polymer such as polyimide, polyethylene, polypropylene,polyethyl teraphthalate (PET), PTFE (Teflon©), PEEK, Tygon, nylon,acetal or other materials, including polymers, semiconductors, ormetals, typically employed in the manufacture of medical devices andproducts.

In further exemplary embodiments, the attachment joint between the lowmodulus and high modulus material may be formed by polymer fusion athigh temperature or pressure, by the use of adhesives such ascyanoacrylate, or by techniques employing surface preparation byelectron bombardment of both materials and then placement of thematerials in contact with each other. All of the above may be used toform leak-free seal joints between the low modulus and high modulusmaterials.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic, perspective view of an intraluminal injectioncatheter suitable for use in the methods and systems of the presentinvention.

FIG. 1B is a cross-sectional view along line 1B-1B of FIG. 1A.

FIG. 1C is a cross-sectional view along line 1C-1C of FIG. 1A.

FIG. 2A is a schematic, perspective view of the catheter of FIGS. 1A-1Cshown with the injection needle deployed.

FIG. 2B is a cross-sectional view along line 2B-2B of FIG. 2A.

FIG. 3 is a schematic, perspective view of the intraluminal catheter ofFIGS. 1A-1C injecting therapeutic agents into an adventitial spacesurrounding a body lumen in accordance with the methods of the presentinvention.

FIG. 4 is a schematic, perspective view of another embodiment of anintraluminal injection catheter useful in the methods of the presentinvention.

FIG. 5 is a schematic, perspective view of still another embodiment ofan intraluminal injection catheter useful in the methods of the presentinvention, as inserted into one of a patient's body lumens.

FIG. 6 is a perspective view of a needle injection catheter useful inthe methods and systems of the present invention.

FIG. 7 is a cross-sectional view of the catheter FIG. 6 shown with theinjection needle in a retracted configuration.

FIG. 8 is a cross-sectional view similar to FIG. 7, shown with theinjection needle laterally advanced into luminal tissue for the deliveryof therapeutic or diagnostic agents according to the present invention.

FIGS. 9A-9E are cross-sectional views of an exemplary fabricationprocess employed to create a free-standing low-modulus patch within ahigher modulus anchor, framework or substrate.

FIGS. 10A-10D are cross-sectional views of the inflation process of anintraluminal injection catheter useful in the methods of the presentinvention.

FIGS. 11A-11C are cross-sectional views of the inflated intraluminalinjection catheter useful in the methods of the present invention,illustrating the ability to treat multiple lumen diameters.

DETAILED DESCRIPTION OF THE INVENTION

By way of example, the first eight figures illustrate a needle injectioncatheter that can benefit from the dual modulus balloon offered by thepresent invention.

As shown in FIGS. 1A-2B, a microfabricated intraluminal catheter 10includes an actuator 12 having an actuator body 12 a and centrallongitudinal axis 12 b. The actuator body more or less forms a C-shapedoutline having an opening or slit 12 d extending substantially along itslength. A microneedle 14 is located within the actuator body, asdiscussed in more detail below, when the actuator is in its unactuatedcondition (furled state) (FIG. 1B). The microneedle is moved outside theactuator body when the actuator is operated to be in its actuatedcondition (unfurled state) (FIG. 2B).

The actuator may be capped at its proximal end 12 e and distal end 12 fby a lead end 16 and a tip end 18, respectively, of a therapeuticcatheter 20. The catheter tip end serves as a means of locating theactuator inside a body lumen by use of a radio opaque coatings ormarkers. The catheter tip also forms a seal at the distal end 12 f ofthe actuator. The lead end of the catheter provides the necessaryinterconnects (fluidic, mechanical, electrical or optical) at theproximal end 12 e of the actuator.

Retaining rings 22 a and 22 b are located at the distal and proximalends, respectively, of the actuator. The catheter tip is joined to theretaining ring 22 a, while the catheter lead is joined to retaining ring22 b. The retaining rings are made of a thin, on the order of 10 to 100microns (μm), substantially flexible but relatively non-distensiblematerial, such as Parylene (types C, D or N), or a metal, for example,aluminum, stainless steel, gold, titanium or tungsten. The retainingrings form a flexible but relatively non-distensible substantially“C”-shaped structure at each end of the actuator. The catheter may bejoined to the retaining rings by, for example, a butt-weld, an ultrasonic weld, integral polymer encapsulation or an adhesive such as anepoxy.

The actuator body further comprises a central, expandable section 24located between retaining rings 22 a and 22 b. The expandable section 24includes an interior open area 26 for rapid expansion when an activatingfluid is supplied to that area. The central section 24 is made of athin, semi-flexible but relatively non-distensible or flexible butrelatively non-distensible, expandable material, such as a polymer, forinstance, Parylene (types C, D or N), silicone, polyurethane orpolyimide. The central section 24, upon actuation, is expandablesomewhat like a balloon-device.

The central section is capable of withstanding pressures of up to about200 psi upon application of the activating fluid to the open area 26.The material from which the central section is made of is flexible butrelatively non-distensible or semi-flexible but relativelynon-distensible in that the central section returns substantially to itsoriginal configuration and orientation (the unactuated condition) whenthe activating fluid is removed from the open area 26. Thus, in thissense, the central section is very much unlike a balloon which has noinherently stable structure.

The open area 26 of the actuator is connected to a delivery conduit,tube or fluid pathway 28 that extends from the catheter's lead end tothe actuator's proximal end. The activating fluid is supplied to theopen area via the delivery tube. The delivery tube may be constructed ofTeflon® or other inert plastics. The activating fluid may be a salinesolution or a radio-opaque dye.

The microneedle 14 may be located approximately in the middle of thecentral section 24. However, as discussed below, this is not necessary,especially when multiple microneedles are used. The microneedle isaffixed to an exterior surface 24 a of the central section. Themicroneedle is affixed to the surface 24 a by an adhesive, such ascyanoacrylate. Alternatively, the microneedle maybe joined to thesurface 24 a by a metallic or polymer mesh-like structure 30 (See FIG.4), which is itself affixed to the surface 24 a by an adhesive. Themesh-like structure may be-made of, for instance, steel or nylon.

The microneedle includes a sharp tip 14 a and a shaft 14 b. Themicroneedle tip can provide an insertion edge or point. The shaft 14 bcan be hollow and the tip can have an outlet port 14 c, permitting theinjection of a pharmaceutical or drug into a patient. The microneedle,however, does not need to be hollow, as it may be configured like aneural probe to accomplish other tasks.

As shown, the microneedle extends approximately perpendicularly fromsurface 24 a. Thus, as described, the microneedle will movesubstantially perpendicularly to an axis of a lumen into which has beeninserted, to allow direct puncture or breach of body lumen walls.

The microneedle further includes a pharmaceutical or drug supplyconduit, tube or fluid pathway 14 d which places the microneedle influid communication with the appropriate fluid interconnect at thecatheter lead end. This supply tube may be formed integrally with theshaft 14 b, or it may be formed as a separate piece that is later joinedto the shaft by, for example, an adhesive such as an epoxy.

The needle 14 may be a 30-gauge, or smaller, steel needle.Alternatively, the microneedle may be microfabricated from polymers,other metals, metal alloys or semiconductor materials. The needle, forexample, may be made of Parylene, silicon or glass. Microneedles andmethods of fabrication are described in U.S. application Ser. No.09/877,653, filed Jun. 8, 2001, entitled “Microfabricated SurgicalDevice”, assigned to the assignee of the subject application, the entiredisclosure of which is incorporated herein by reference.

The catheter 20, in use, is inserted through an opening in the body(e.g. for bronchial or sinus treatment) or through a percutaneouspuncture site (e.g. for artery or venous treatment) and moved within apatient's body passageways 32, until a specific, targeted region 34 isreached (see FIG. 3). The targeted region 34 may be the site of tissuedamage or more usually will be adjacent the sites typically being within100 mm or less to allow migration of the therapeutic or diagnosticagent. As is well known in catheter-based interventional procedures, thecatheter 20 may follow a guide wire 36 that has previously been insertedinto the patient. Optionally, the catheter 20 may also follow the pathof a previously-inserted guide catheter (not shown) that encompasses theguide wire.

During maneuvering of the catheter 20, well-known methods of fluoroscopyor magnetic resonance imaging (MRI) can be used to image the catheterand assist in positioning the actuator 12 and the microneedle 14 at thetarget region. As the catheter is guided inside the patient's body, themicroneedle remains unfurled or held inside the actuator body so that notrauma is caused to the body lumen walls.

After being positioned at the target region 34, movement of the catheteris terminated and the activating fluid is supplied to the open area 26of the actuator, causing the expandable section 24 to rapidly unfurl,moving the microneedle 14 in a substantially perpendicular direction,relative to the longitudinal central axis 12 b of the actuator body 12a, to puncture a body lumen wall 32 a. It may take only betweenapproximately 100 milliseconds and five seconds for the microneedle tomove from its furled state to its unfurled state.

The ends of the actuator at the retaining rings 22 a and 22 b remainfixed to the catheter 20. Thus, they do not deform during actuation.Since the actuator begins as a furled structure, its so-called pregnantshape may exist as an unstable buckling mode. This instability, uponactuation, may produce a large-scale motion of the microneedleapproximately perpendicular to the central axis of the actuator body,causing a rapid puncture of the body lumen wall without a large momentumtransfer. As a result, a microscale opening is produced with veryminimal damage to the surrounding tissue. Also, since the momentumtransfer is relatively small, only a negligible bias force is requiredto hold the catheter and actuator in place during actuation andpuncture.

The microneedle aperture, in fact, travels with such force that it canenter body lumen tissue 32 b as well as the adventitia, media, or intimasurrounding body lumens. Additionally, since the actuator is “parked” orstopped prior to actuation, more precise placement and control overpenetration of the body lumen wall are obtained.

After actuation of the microneedle and delivery of the agents to thetarget region via the microneedle, the activating fluid is exhaustedfrom the open area 26 of the actuator, causing the expandable section 24to return to its original, furled state. This also causes themicroneedle to be withdrawn from the body lumen wall. The microneedle,being withdrawn, is once again sheathed by the actuator.

Various microfabricated devices can be integrated into the needle,actuator and catheter for metering flows, capturing samples ofbiological tissue, and measuring pH. The device 10, for instance, couldinclude electrical sensors for measuring the flow through themicroneedle as well as the pH of the pharmaceutical being deployed. Thedevice 10 could also include an intravascular ultrasonic sensor (IVUS)for locating vessel walls, and fiber optics, as is well known in theart, for viewing the target region. For such complete systems, highintegrity electrical, mechanical and fluid connections are provided totransfer power, energy, and pharmaceuticals or biological agents withreliability.

By way of example, the microneedle may have an overall length of betweenabout 200 and 3,000 microns (μm). The interior cross-sectional dimensionof the shaft 14 b and supply tube 14 d may be on the order of 20 to 250um, while the tube's and shaft's exterior cross-sectional dimension maybe between about 100 and 500 μm. The overall length of the actuator bodymay be between about 5 and 50 millimeters (mm), while the exterior andinterior cross-sectional dimensions of the actuator body can be betweenabout 0.4 and 4 mm, and 0.5 and 5 mm, respectively. The gap or slitthrough which the central section of the actuator unfurls may have alength of about 4-40 mm, and a cross-sectional dimension of about 50-500μm. The diameter of the delivery tube for the activating fluid may beabout 100 μm. The catheter size may be between 1.5 and 15 French (Fr).

Variations of the invention include a multiple-buckling actuator with asingle supply tube for the activating fluid. The multiple-bucklingactuator includes multiple needles that can be inserted into or througha lumen wall for providing injection at different locations or times.

For instance, as shown in FIG. 4, the actuator 120 includes microneedles140 and 142 located at different points along a length or longitudinaldimension of the central, expandable section 240. The operating pressureof the activating fluid is selected so that the microneedles move at thesame time. Alternatively, the pressure of the activating fluid may beselected so that the microneedle 140 moves before the microneedle 142.

Specifically, the microneedle 140 is located at a portion of theexpandable section 240 (lower activation pressure) that, for the sameactivating fluid pressure, will buckle outwardly before that portion ofthe expandable section (higher activation pressure) where themicroneedle 142 is located. Thus, for example, if the operating pressureof the activating fluid within the open area of the expandable section240 is two pounds per square inch (psi), the microneedle 140 will movebefore the microneedle 142. It is only when the operating pressure isincreased to four psi, for instance, that the microneedle 142 will move.Thus, this mode of operation provides staged buckling with themicroneedle 140 moving at time t₁, and pressure p₁, and the microneedle142 moving at time t₂ and p₂, with t₁, and p₁, being less than t₂ andp₂, respectively.

This sort of staged buckling can also be provided with differentpneumatic or hydraulic connections at different parts of the centralsection 240 in which each part includes an individual microneedle.

Also, as shown in FIG. 5, an actuator 220 could be constructed such thatits needles 222 and 224A move in different directions. As shown, uponactuation, the needles move at angle of approximately 90° to each otherto puncture different parts of a lumen wall. A needle 224B (as shown inphantom) could alternatively be arranged to move at angle of about 180°to the needle 224A.

The above catheter designs and variations thereon, are described inpublished U.S. Patent Application Nos. 2003/005546 and 2003/0055400, thefull disclosures of which are incorporated herein by reference.Co-pending application Ser. No. 10/350,314, assigned to the assignee ofthe present application, describes the ability of substances deliveredby direct injection into the adventitial and pericardial tissues of theheart to rapidly and evenly distribute within the heart tissues, even tolocations remote from the site of injection. The full disclosure of thatco-pending application is also incorporated herein by reference. Analternative needle catheter design suitable for delivering thetherapeutic or diagnostic agents of the present invention will bedescribed below. That particular catheter design is described andclaimed in co-pending application Ser. No. 10/397,700 (Attorney DocketNo. 021621-001500 US), filed on Mar. 19, 2003, the full disclosure ofwhich is incorporated herein by reference.

Referring now to FIG. 6, a needle injection catheter 310 constructed inaccordance with the principles of the present invention comprises acatheter body 312 having a distal end 314 and a proximal 316. Usually, aguide wire lumen 313 will be provided in a distal nose 352 of thecatheter, although over-the-wire and embodiments which do not requireguide wire placement will also be within the scope of the presentinvention. A two-port hub 320 is attached to the proximal end 316 of thecatheter body 312 and includes a first port 322 for delivery of ahydraulic fluid, e.g., using a syringe 324, and a second port 326 fordelivering the pharmaceutical agent, e.g., using a syringe 328. Areciprocatable, deflectable needle 330 is mounted near the distal end ofthe catheter body 312 and is shown in its laterally advancedconfiguration in FIG. 6.

Referring now to FIG. 7, the proximal end 314 of the catheter body 312has a main lumen 336 which holds the needle 330, a reciprocatable piston338, and a hydraulic fluid delivery tube 340. The piston 338 is mountedto slide over a rail 342 and is fixedly attached to the needle 330.Thus, by delivering a pressurized hydraulic fluid through a lumen 341tube 340 into a bellows structure 344, the piston 338 may be advancedaxially toward the distal tip in order to cause the needle to passthrough a deflection path 350 formed in a catheter nose 352.

As can be seen in FIG. 8, the catheter 310 may be positioned in acoronary blood vessel BV, over a guide wire GW in a conventional manner.Distal advancement of the piston 338 causes the needle 330 to advanceinto luminal tissue T adjacent to the catheter when it is present in theblood vessel. The therapeutic or diagnostic agents may then beintroduced through the port 326 using syringe 328 in order to introducea plume P of agent in the cardiac tissue, as illustrated in FIG. 8. Theplume P will be within or adjacent to the region of tissue damage asdescribed above.

The needle 330 may extend the entire length of the catheter body 312 or,more usually, will extend only partially into the therapeutic ordiagnostic agents delivery lumen 337 in the tube 340. A proximal end ofthe needle can form a sliding seal with the lumen 337 to permitpressurized delivery of the agent through the needle.

The needle 330 will be composed of an elastic material, typically anelastic or super elastic metal, typically being nitinol or other superelastic metal. Alternatively, the needle 330 could be formed from anon-elastically deformable or malleable metal which is shaped as itpasses through a deflection path. The use of non-elastically deformablemetals, however, is less preferred since such metals will generally notretain their straightened configuration after they pass through thedeflection path.

The bellows structure 344 may be made by depositing by parylene oranother conformal polymer layer onto a mandrel and then dissolving themandrel from within the polymer shell structure. Alternatively, thebellows 344 could be made from an elastomeric material to form a balloonstructure. In a still further alternative, a spring structure can beutilized in, on, or over the bellows in order to drive the bellows to aclosed position in the absence of pressurized hydraulic fluid therein.

After the therapeutic material is delivered through the needle 330, asshown in FIG. 8, the needle is retracted and the catheter eitherrepositioned for further agent delivery or withdrawn. In someembodiments, the needle will be retracted simply by aspirating thehydraulic fluid from the bellows 344. In other embodiments, needleretraction may be assisted by a return spring, e.g., locked between adistal face of the piston 338 and a proximal wall of the distal tip 352(not shown) and/or by a pull wire attached to the piston and runningthrough lumen 341.

FIGS. 9A-9E illustrate an exemplary process for fabricating a dualmodulus balloon structure or anchored membrane structure in accordancewith the principles of the present invention. The first step of thefabrication process is seen in FIG. 9A, in which a low modulus “patch”,or membrane, material 400 is layered between removable (e.g.dissolvable) substrates 401 and 402. The substrate 401 covers one entireface of the patch 400, while the substrate 402 covers only a portion ofthe opposite face, leaving an exposed edge or border region about theperiphery.

In FIG. 9B, a layer of a “flexible but relatively non-distensible”material 403 is deposited onto one side of the sandwich structure fromFIG. 9A to provide a frame to which the low-modulus patch is attached.This material may be, for example, parylene N, C, or D, though it can beone of many other polymers or metals. When the flexible but relativelynon-distensible material is parylene and the patch material is asilicone or siloxane polymer, a chemomechanical bond is formed betweenthe layers, creating a strong and leak-free joint between the twomaterials. The joint formed between the two materials usually has a peelstrength or interfacial strength of at least 0.05 N/mm², typically atleast 0.1 N/mm², and often at least 0.2 N/mm².

In FIG. 9C, the “flexible but relatively non-distensible” frame oranchor material 403 has been trimmed or etched to expose the substratematerial 402 so that it can be removed. Materials 401 and 402 may bedissolvable polymers that can be removed by one of many chemicalsolvents. In FIG. 9D, the materials 401 and 402 have been removed bydissolution, leaving materials 400 and 403 joined edge-to-edge to formthe low modulus, or elastomeric, patch 400 within a frame of generallyflexible but relatively non-distensible material 403.

As shown in FIG. 9E, when positive pressure +ΔP is applied to one side405 of the structure, the non-distensible frame 403 deforms onlyslightly, while the elastomeric patch 400 deforms much more. The lowmodulus material may have a material modulus which is always lower thanthat of the high modulus material and is typically in the range from 0.1to 1,000 MPa, more typically in the range from 1 to 250 MPa. The highmodulus material may have a material modulus in the range from 1 to50,000 MPa, more typically in the range from 10 to 10,000 MPa. Thematerial thicknesses may range in both cases from approximately 1 micronto several millimeters, depending on the ultimate size of the intendedproduct. For the treatment of most body lumens, the thicknesses of bothmaterial layers 402 and 403 are in the range from 10 microns to 2 mm.

Referring to FIGS. 10A-10D, the elastomeric patch of FIGS. 9A-9D isintegrated into the intraluminal catheter of FIG. 1-5. In FIG. 10A-D,the progressive pressurization of such a structure is displayed in orderof increasing pressure. In FIG. 10A, the balloon is placed within a bodylumen L. The lumen wall W divides the lumen from periluminal tissue T,or adventitia A*, depending on the anatomy of the particular lumen. Thepressure is neutral, and the non-distensible structure forms a U-shapedinvoluted balloon 12 similar to that in FIG. 1 in which a needle 14 issheathed. While a needle is displayed in this diagram, other workingelements including cutting blades, laser or fiber optic tips,radiofrequency transmitters, or other structures could be substitutedfor the needle. For all such structures, however, the elastomeric patch400 will usually be disposed on the opposite side of the involutedballoon 12 from the needle 14.

Actuation of the balloon 12 occurs with positive pressurization. In FIG.10B, pressure (+ΔP₁) is added, which begins to deform the flexible butrelatively non-distensible structure, causing the balloon involution tobegin its reversal toward the lower energy state of a round pressurevessel. At higher pressure +ΔP₂ in FIG. 10C, the flexible but relativelynon-distensible balloon material has reached its rounded shape and theelastomeric patch has begun to stretch. Finally, in FIG. 10D at stillhigher pressure +ΔP₃, the elastomeric patch has stretched out toaccommodate the full lumen diameter, providing an opposing force to theneedle tip and sliding the needle through the lumen wall and into theadventitia. Typical dimensions for the body lumens contemplated in thisfigure are between 0.1 mm and 50 mm, more often between 0.5 mm and 20mm, and most often between 1 mm and 10 mm. The thickness of the tissuebetween the lumen and adventitia is typically between 0.001 mm and 5 mm,more often between 0.01 mm and 2 mm and most often between 0.05 mm and 1mm. The pressure +ΔP useful to cause actuation of the balloon istypically in the range from 0.1 atmospheres to 20 atmospheres, moretypically in the range from 0.5 to 20 atmospheres, and often in therange from 1 to 10 atmospheres.

As illustrated in FIGS. 11A-11C, the dual modulus structure formedherein provides for low-pressure (i.e., below pressures that may damagebody tissues) actuation of an intraluminal medical device to placeworking elements such as needles in contact with or through lumen walls.By inflation of a constant pressure, and the elastomeric material willconform to the lumen diameter to provide full apposition. Dual modulusballoon 12 is inflated to a pressure +ΔP₃ in three different lumendiameters in FIGS. 11A, 11B, and 11C. for the progressively largerinflation of patch 400 provides optimal apposition of the needle throughthe vessel wall regardless of diameter. Thus, a variable diameter systemis created in which the same catheter may be employed in lumensthroughout the body that are within a range of diameters. This is usefulbecause most medical products are limited to very tight constraints(typically within 0.5 mm) in which lumens they may be used. A system asdescribed in this invention may accommodate several millimeters ofvariability in the luminal diameters for which they are useful.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

1. A supported membrane structure comprising: an elastomeric membranecomponent; and a flexible but relatively non-distensible frame componentsupporting the membrane component; wherein the frame component is formedby vapor deposition onto the elastomeric membrane component.
 2. Amembrane structure as in claim 1, wherein the elastomeric membranecomponent is comprised of a polymer selected from the group consistingof silicone, neoprene, silastic, chronoprene, latex, siloxane, andpolyether block amide.
 3. A membrane structure as in claim 2, whereinthe flexible but relatively non-distensible anchor component is formedfrom a polymer selected from the group consisting of parylene,polyimide, polyethylene, polypropylene, polytetrafluoroethylene, nylon,and polyether ether ketone.
 4. A membrane structure as in claim 1,wherein the elastomeric membrane component comprises a silicone materialand the flexible but relatively non-distensible anchor componentcomprises a parylene material.
 5. A membrane structure as in claim 1,wherein an interfacial region between the components has an interfacialstrength of at least 0.1 N/mm2.
 6. A membrane structure as in claim 5,wherein the seal formed between the two components does not leak below100 kPa of pressure.
 7. A membrane structure as in claim 1, wherein theframe component completely circumscribes the membrane component.